The title of this renewal application has been changed due to enlargment in the scope. The overall objective of this research is to establish the relationship between the geneitc apparatus (DNA sequence organization and gene expression) and mutagenesis/carcinogenesis as the basis of the assessment of the biomedical risks caused by the environmental mutagens/carcinogens. Considerable progress toward this goal has been made in the past three years. The objective is to be achieved by: 1) the additional acquisition/establishment of knowledge/methodology for the characterization of carcinogenesis with special emphasis on promotion and demotion; 2) by defining the relationship between mutagenesis and carcinogenesis, with special emphasis on the development of somatic mutation markers closely related to neoplasia; 3) by development of special perturbation only to DNA (or portion of DNA) leading to carcinogenesis/somatic mutagenesis; 4) by analysis of the genetic nature of neoplasia through somatic genetics techniques; 5) by comparison of the alteration in phenotypes and genetic apparatus of tumor cells form both fibroblasts and epithelial cells; 6) by analysis of the basic mechanism in the neoplastic transformation induced by Herpes simplex virus or HSV-DNA; 7) by comparing basic mechanisms in carcinogenesis initiated by physical, chemical and viral agents; 8) by defining the alteration of the genetic apparatus (DNA sequence and RNA sequence) in mutagenesis/carcinogenesis. The above achievements will lead to the identification and location of the target DNA sequences most sensitive or susceptible in carcinogenesis/mutagenesis, as well as the indication of the malfunctioning of the genetic apparatus through the appearance of RNA bearing previously quiescent DNA sequences. This study will also be extended for the Syrian hamster cells to the human cells. This will provide the basic science about carcinogenesis/mutagenesis needed for the establishment of a biomedical risk assessment system for the environmental mutagens/carcinogens.